Tumor Necrosis Factor delta (TNF-delta; APRIL) is a member of the tumor necrosis factor (“TNF”) superfamily that induces both in vivo and in vitro B cell proliferation and differentiation (See e.g. U.S. Patent Application Nos. 60/016,812; 60/211,537; 60/241,952; 60/254,875; 60/277,978; and Ser. No. 08/815,783 (now U.S. Pat. No. 6,509,170); and International Publication No. WO97/33902; and Yu et al., Nature Immunol. 1(3):252–256 (2000)). APRIL is distinguishable from other B cell growth and differentiation factors such as IL-2, IL-4, IL-5, IL-6, IL-7, IL-13, IL-15, CD40L, or CD27L (CDT0) by its monocyte-specific gene and protein expression pattern and its specific receptor distribution and biological activity on B lymphocytes. APRIL expression is not detected in natural killer (“NK”) cells, T cells or B cells, but is restricted to cells of myeloid origin. The gene encoding APRIL has been mapped to chromosome 17p13.
APRIL is expressed as a 250 amino acid type II membrane-bound polypeptide and a soluble 146 amino acid polypeptide (SEQ ID NO:37). The NH2-terminus of the soluble form of APRIL begins at Ala88 of SEQ ID NO:36 (which is equivalent to Ala 105 of SEQ ID NO:37). Soluble recombinant APRIL has been shown to induce in vitro proliferation of murine splenic B cells and to bind to a cell-surface receptor on these cells and also on T cells (Yu et al., 2000 supra). Soluble APRIL administration to mice has been shown to result in an increase in B cell numbers in the spleen and mesenteric lymph node, and an increase in serum IgM levels (Yu et al., 2000 supra).
Based upon its expression pattern and biological activity, APRIL has been suggested to be involved in the exchange of signals between B cells, T cells and monocytes or their differentiated progeny. As such, antibodies and related molecules that immunospecifically bind to APRIL may find medical utility in, for example, the treatment of B cell disorders and T cell disorders associated with for example autoimmunity, neoplasia, or immunodeficiency syndromes.